Biochemistry, Substance P

Substance P is a neuropeptide made up of 11 amino acids—an undecapeptide—and is a part of the tachykinin neuropeptide family. Its receptor, neurokinin type 1 (NK-1R), is a transmembrane bound receptor on many cell types in the body including the endothelium of the blood vessels and lymphatics, white blood cells (WBCs), fibroblasts and neurons. Substance P's most well-known function is as a neurotransmitter and a modulator of pain perception by altering cellular signaling pathways. Additionally, substance P plays a role in gastrointestinal functioning, memory processing, angiogenesis, vasodilation, and cell growth and proliferation. Substance P works by altering cellular signaling pathways primarily through G-protein coupled receptors acting through both the IP3/DAG and cAMP second messenger systems, depending on the cell type. Clinically, research into substance P has led to the development of antiemetic medications called NK-1R/substance P antagonists. These are primarily used to control chemotherapy-induced vomiting by preventing the binding of substance P to NK1 receptors in the area postrema--the area in the brain that controls emesis. Substance P is also a key molecule in the neurogenic inflammation response, a critical interaction between the nervous system and the immune system. Additionally, the function of substance P is involved in the pathogenesis of various diseases including but not limited to cancer, diabetes, rheumatoid arthritis, myocarditis, heart failure, epilepsy, migraine, thrombosis, pruritus, depression, and anxiety.